The program project is focused on the structure and function of abnormal hemoglobins and the red cell and their interactions in disease. We are studying the structure of hemoglobin in solution, trying to characterize its conformational states in respect to overall motility and subunit interaction. We utilize the reactivity of groups on protein surface, the roles of isotope exchange, calorimetric studies of protein-protein association, dimer-tetramer equilibrium, and thermo dynamics of ligand binding. We are studying the role water-protein interactions play in hemoglobin function. We are studying the symmetry of the heme surrounding by magnetic circular dichroism. We are using all the above approaches to compare the behavior of hemoglobin SO to that of hemoglobin AO. We are probing the role of calcium dependent tranformations of red cell membrane proteins. We are investigating the role of such transition in formation irreversibly sickled cells. We are studying model systems of red cells where we can regulate the Ca ions flux and membrane permeability with ionophor. We are investigating the change in red cell metabolism in case of malarial infections. We are further studying, in a collaborative effort, utilization of a class of new anti-sickling agents based on the family of maleimide derivatives. We are concurrently developing EM probes to detect distribution of Calcium in intact cells and we are also involved in construction of new types of rheological devices to measure red cell behavior.